Renal macrophages induce hypertension and kidney fibrosis in Angiotensin II salt mice model

Joseph Kasyoki Peter; Ryusuke Umene; Chia-Hsien Wu; Yasuna Nakamura; Norito Washimine; Ryoko Yamamoto; Caroline Ngugi; Kavoo Linge; Joseph K Kweri; Tsuyoshi Inoue

doi:10.1016/j.bbrc.2024.149997

Renal macrophages induce hypertension and kidney fibrosis in Angiotensin II salt mice model

Biochem Biophys Res Commun. 2024 Jun 30:715:149997. doi: 10.1016/j.bbrc.2024.149997. Epub 2024 Apr 24.

Authors

Affiliations

¹ Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Japan; Department of Medical Physiology, School of Medicine, Jomo Kenyatta University of Agriculture and Technology, Kenya; Department of Clinical Medicine, School of Medicine, Jomo Kenyatta University of Agriculture and Technology, Kenya.
² Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Japan; Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Japan. Electronic address: rumene@nagasaki-u.ac.jp.
³ Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
⁴ Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Japan; Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Japan.
⁵ Department of Medical Microbiology, School of Biomedical Sciences, Jomo Kenyatta University of Agriculture and Technology, Kenya.
⁶ Department of Medical Physiology, School of Medicine, Jomo Kenyatta University of Agriculture and Technology, Kenya.
⁷ Department of Human Anatomy, School of Medicine, Jomo Kenyatta University of Agriculture and Technology, Kenya.
⁸ Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Japan. Electronic address: ts-inoue@nagasaki-u.ac.jp.

PMID: 38678782
DOI: 10.1016/j.bbrc.2024.149997

Abstract

The immune system is involved in hypertension development with different immune cells reported to have either pro or anti-hypertensive effects. In hypertension, immune cells have been thought to infiltrate blood pressure-regulating organs, resulting in either elevation or reduction of blood pressure. There is controversy over whether macrophages play a detrimental or beneficial role in the development of hypertension, and the few existing studies have yielded conflicting results. This study aimed to determine the effects of angiotensin II (Ang II) salt-induced hypertension on renal immune cells and to determine whether renal macrophages are involved in the induction of hypertension. Hypertension was induced by administration of Ang II and saline for two weeks. The effects of hypertension on kidney immune cells were assessed using flow cytometry. Macrophage infiltration in the kidney was assessed by immunohistochemistry and kidney fibrosis was assessed using trichrome stain and kidney real time-qPCR. Liposome encapsulated clodronate was used to deplete macrophages in C57BL/6J mice and investigate the direct role of macrophages in hypertension induction. Ang II saline mice group developed hypertension, had increased renal macrophages, and had increased expression of Acta2 and Col1a1 and kidney fibrotic areas. Macrophage depletion blunted hypertension development and reduced the expression of Acta2 and Col1a1 in the kidney and kidney fibrotic areas in Ang II saline group. The results of this study demonstrate that macrophages infiltrate the kidneys and increase kidney fibrosis in Ang II salt-induced hypertension, and depletion of macrophages suppresses the development of hypertension and decreases kidney fibrosis. This indicates that macrophages play a direct role in hypertension development. Hence macrophages have a potential to be considered as therapeutic target in hypertension management.

Keywords: Angiotensin II; Hypertension; Immune system; Renal fibrosis; Renal macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin II* / pharmacology
Animals
Blood Pressure / drug effects
Disease Models, Animal*
Fibrosis*
Hypertension* / chemically induced
Hypertension* / metabolism
Hypertension* / pathology
Kidney Diseases / chemically induced
Kidney Diseases / etiology
Kidney Diseases / metabolism
Kidney Diseases / pathology
Kidney* / drug effects
Kidney* / metabolism
Kidney* / pathology
Macrophages* / drug effects
Macrophages* / metabolism
Macrophages* / pathology
Male
Mice
Mice, Inbred C57BL*
Sodium Chloride, Dietary / adverse effects

Substances

Angiotensin II
Sodium Chloride, Dietary